Odors play an increasingly appreciated role in our general quality of life and well being, a role that is compromised by the effect of disease, drugs, aging and environmental onslaught on olfactory competence. Primary olfactory receptor neurons serve the critical function of detecting and transducing odor stimuli. Disruption of any of the cellular processes leading to receptor cell activation would impair olfactory function. Our laboratory maintains an ongoing NIH-funded research program on mechanisms of olfactory transduction built around the lobster as an animal model. Using insight gained from the lobster model, we hypothesized that by exploring the potential involvement of the 3-phosphoinositide pathway we could implicate phosphoinositide signaling in mammals. In doing so, we would re-visit the important, but controversial question of the role, if any, of phosphoinositide signaling in mammalian olfactory transduction. Preliminary data obtained in collaboration with another laboratory support that contention. We propose to develop this important finding into a separate line of investigation built around mammalian models, specifically mouse and rat. As this is the first venture of our laboratory into mammalian models, we feel it prudent to better document our ability to work with mammalian models before submitting this line of investigation as an R01. This new, exciting line of investigation should have high impact on the field, making it competitive for R01 funding once the proposed additional preliminary data are in hand.